Two studies are proposed and both involve continuation of ongoing work. The first study concerns the affective and cognitive consequences of ECT in 100 patients presenting primary, major depressive disorder. Patients will be randomly assigned to four ECT treatment conditions, crossing the factors of low and high ECT dosage and modality (unilateral right and bilateral electrode placements). Treatment responders enter a double-blind drug continuation trial, contrasting nortriptyline and placebo. At pretreatment, postsixth ECT, posttreatment and 2-month followup a battery of neuropsychological, neurophysiological, and neuroendocrinological procedures will be administered. Acute cognitive effects will be examined at each treatment. Normal controls will be tested on major portions of the battery. The primary aims are (1) to determine dose/response relations as a function of modality for the affective and cognitive consequences of ECT; (2) to identify pretreatment neuropsychological and neurophysiological abnormalities in depressed patients and the effects of treatment conditions on such abnormalities; (3) to evaluate a new method of ECT administration and to better characterize the nature and effects of electrical stimulation; (4) to determine the risk/benefits of postECT continuation medication in patients largely medication resistant during the acute phase of illness. The second study concerns the treatment of acute manic episodes. Patients (n=75) will be randomly assigned to intensive pharmacotherapy with combination lithium/neuroleptic treatment or to unilateral left, unilateral right, or bilateral ECT conditions, after establishing resistance to preentry pharmacotherapy. The primary aims are (1) to determine rates of therapeutic response to the four acute treatment conditions, with the hypothesis that among the ECT conditions, left and bilateral ECT will be superior in efficacy to unilateral right ECT; (2) to identify neurophysiological and biochemical abnormalities in regional cerebral blood flow and brain electrical activity in acute manic episodes and the effects of treatment conditions on such abnormalities.